1. Field of the Invention
The present invention relates generally to biological materials that are resistant to in vivo calcification. More particularly, the present invention relates to the treatment of biocompatible natural materials, such as porcine heart valves, bovine pericardium, porcine pericardium and equine pericardium with dimethyl sulfoxide as the anticalcification agent. In particular, the present invention relates to treatment of the above biocompatible materials which have been, or are to be, treated by fixation in a glutaraldehyde solution, with dimethyl sulfoxide as the anticalcification agent.
2. Description of the Related Art
Cardiac valve replacement remains the major alternative in the treatment of severely diseased heart valves. Valve replacements can be from various sources and of various designs, all intended to imitate the function of the natural human heart valve. Currently, the major types of valve replacements are mechanical heart valves, bioprosthetic heart valves, and aortic homografts.
The mechanical valves in use today are of various designs and materials. Their performance in vivo have been shown to be good and reliable. However, their attributes are often offset by complications that can arise with the use of this type of valve, mainly thrombosis, which, if untreated, can lead to valvular failure. The possibility of thrombosis often requires patients receiving this type of valve to receive anticoagulant treatment, a lifetime inconvenience. Furthermore, catastrophic failure, which is a situation where the material used to make the component that controls blood flow breaks, is an occasional high risk factor.
In contrast, bioprosthetic heart valves, typically fabricated from porcine aortic valves or bovine pericardium, have better hemodynamics than mechanical valves, in that they provide blood flow characteristics closely approximating physiological blood flow. Moreover, in most cases, bioprosthetic valves do not require patients to be on anticoagulation treatment because thrombosis is unlikely. However, prolonged residence in vivo has lead to calcification of the valve material, in particular where the bioprosthetic valve has been prepared by a process involving glutaraldehyde fixing. This calcification can lead to the clinical failure of bioprosthetic heart valves, at a failure rate that is higher for younger patients. Therefore, the use of bioprosthetic heart valves has been limited because of the susceptibility of the biomaterial to calcification. Similarly, human aortic homograft implants have also been observed to undergo calcification involving the valvular tissue as well as the adjacent aortic wall.
Nevertheless, the favorable features of the bioprosthetic heart valve make it a desirable candidate for continued use.
Bioprosthetic heart valves are typically fabricated by a process including fixation of the biocompatible material, usually bovine pericardium or porcine aortic valves, in glutaraldehyde solution, which functions as a tissue preservative. This glutaraldehyde solution has been indicated as a possible major contributor to biomaterial calcification. It is believed that glutaraldehyde is released from the biomaterial after implantation, which leads to a local cytotoxic environment. This cytotoxic environment leads to the presence of cellular debris, which may provide starting points for calcification.
However, attempts to replace the glutaraldehyde fixation process have been unsuccessful to date, and glutaraldehyde fixation remains the method of choice for preserving tissue and preparing it for implantation as a biomaterial.
Efforts to improve the long-term inhibition of calcification via incorporation of anticalcification agents have also been unsuccessful to date. For example, treatment with Fe(III) has been unsuccessful due to diffusion of the Fe(III) out of the treated tissue. Similar problems can be expected to be encountered with Al(III), as well as potential side effects, such as mental disorders, associated with aluminum.
As a result, there remains a need for a method of long-term calcification prevention suitable for use with glutaraldehyde fixed bioprosthetic heart valves and similar implant devices, such as arterial grafts and other tubular duct replacements prepared from arteries, veins, human umbilical cords, etc.